Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Earlier results on potassium ion inhibition of amino acid incorporation into the brain proteins in vivo (spreading cortical depression) led to the hypothesis that inhibition of protein synthesis is based on ATP deficiency. In the present study we tested various aspects of the aminocylation of tRNA, an ATP-dependent process, during spreading cortical depression produced by the topical application of 25% KCl. On using a 7-min interval between the subcutaneous injection of L-[U-14C] leucine and killing the rat, incorporation into the tRNA fraction was found to be reduced by 25%. Total amino acid radioactivity in the soluble fraction was unaltered. The acceptor capacity of tRNA, measured in vitro, and the proportion of non-acylated tRNA in vivo were likewise unchanged.
 ...
PMID:On the mechanism of the inhibitory effect of potasium ions on amino acid incorporation into rat cerebral cortex proteins in vivo. 14 13

Growth of Escherichia coli AB 2271 under threonine or isoleucine deficiency leads to a depression of the threonyl-tRNA synthetase and isoleucyl-tRNA synthetase respectively. During this amino-acid-limited growth the concentrations of isoaccepting fractions of the cognate tRNA species were changed, as demonstrated by their altered reversed-phase-5 chromatograms. But, in addition, the profiles of the isoacceptors of all other tRNA species investigated, i.e. of tRNAsLeu, tRNAsSer and tRNAsArg were also altered. This means that, if there is a correlation between regulation of the level of an aminoacyl-tRNA synthetase and its cognate isoaccepting tRNAs, it is superimposed by the effect of amino acid limitation upon the concentration of all isoaccepting tRNAs. So far drastic changes in profiles of isoaccepting tRNAs have only been observed under unbalanced growth in relaxed cells or during treatment with antibiotics. Here we demonstrate that similar heavy alterations in patterns of isoaccepting tRNAs occur in a proven stringent E. coli strain growing exponentially under amino acid limitation. Thus the observed changes in the profiles of isoaccepting tRNAs during amino acid limitation signal a meaningful biological function of those newly or increasingly occurring isoaccepting tRNAs. During the growth under amino acid limitation the total acceptor activity of eight investigated tRNA species, however, stayed unchanged, except that under threonine-limited growth the total amount of tRNAIle was reduced to about half and that of tRNAGlu increased; both tRNA species of these isoacceptors are known [30,31] as spacers between ribosomal RNAs.
 ...
PMID:Alteration of the intracellular concentration of aminoacyl-tRNA synthetases and isoaccepting tRNAs during amino-acid limited growth in Escherichia coli. 34 70

The synthesis of at least six enzymes implicated in methionine biosynthesis in Saccharomyces cerevisiae is regulated pleiotropically by two independent regulatory systems. Repression of enzyme synthesis is promoted either by exogenous methonine or by exogenous S-adenosylmethionine (SAM). The regulatory system acting in methionine mediated repression seems to comprise methionyl-tRNA-met as a co-repressor and the other system, acting in SAM repression, comprises SAM as a co-repressor. This concept gives a role in regulation to the two activated forms of methionine. Moreover, evidence is presented that the "SAM repressor" probably acts at a post-transcriptional level while the "met-tRNAmet repressor" would be active at the transcriptional level. These conclusions have been based on two series of experiments: one using a mutant bearing a modified methionyl-tRNA synthetase [L-methionine: tRNA-met ligase (AMP-forming) E.C.6.1.1.10] and one studying the kinetics of depression of synthesis of one of the biosynthetic enzymes after repression either by exogenous methionine or by exogenous SAM. Our results are strengthened by the use of two different drugs: one inhibiting messenger RNA synthesis and the other inhibiting protein synthesis.
 ...
PMID:Regulation of methionine synthesis in Saccharomyces cerevisiae operates through independent signals: methionyl-tRNAmet and S-adenosylmethionine. 78 67

This study was undertaken to determine whether regular endurance running, of the type known to attenuate glucocorticoid-induced muscle atrophy, produces a reversal of the glucocorticoid-mediated suppression of myosin heavy chain (MHC) synthesis. Female rats were arbitrarily assigned to one of four groups. There were two sedentary groups that received either a vehicle (1% aqueous carboxymethyl cellulose) or cortisol acetate (100 mg/kg body wt) for 11 consecutive days and two exercise (treadmill running 29 m/min, 90 min/day, for 11 consecutive days) groups that received the activity simultaneously with either vehicle or steroid treatments. Protein synthesis measurements were performed by constant infusion of [3H]leucine. Fractional synthesis rates of MHC were determined from the leucyl-tRNA precursor pool, which was similar in all groups (range 2.85 +/- 0.32 to 3.51 +/- 0.43 dpm/pmol). Exercise prevented 30% of the plantaris muscle mass loss as the result of cortisol acetate treatment. MHC synthesis rates (%/day) in plantaris muscles of sedentary animals were reduced by glucocorticoid treatment to 65% (6.2/9.5) of the vehicle-treated group. Exercise did not alter this depression of MHC synthesis. The combination of exercise and glucocorticoid treatment reduced the calculated MHC breakdown rate (%/day) to 80% (-8.0/-10.1) of the rate resulting from hormone treatment alone and 60% (-8.0/-13.3) of the rate resulting from exercise alone. These results show that endurance exercise does not reverse the glucocorticoid inhibition of MHC synthesis in muscle but may act through reducing MHC breakdown.
 ...
PMID:Myosin heavy chain turnover and glucocorticoid deterrence by exercise in muscle. 260 37

The goal of these studies was to evaluate acute changes in protein metabolism in skeletal muscle in response to contractile activity. Rates of protein synthesis were measured by following L-[U-14C]phenylalanine incorporation into protein in muscles of the perfused rat hindlimb at rest, during 10 min of maximal isometric muscle contractions, and during 10 min of recovery. Synthesis measurements were carried out under conditions that ensured that the specific radioactivity of the tRNA-bound precursor amino acid was equal to that of extracellular phenylalanine. Protein degradation was estimated by measuring the release of Nt-methylhistidine. Rates of synthesis were markedly inhibited in response to muscle contractions in tibialis anterior, gastrocnemius, and plantaris but were unaffected in soleus. Rates of synthesis returned toward those observed in the resting condition during the recovery period. Rates of degradation were also markedly inhibited in response to muscle contractions. Decreased rates of synthesis correlated with reduced tissue contents of ATP and creatine phosphate, a reduced ATP/ADP, and an elevated tissue content of lactate. The results demonstrate that isometric contractions in muscles consisting of a high proportion of fast glycolytic fibers result in a marked depression in rates of protein synthesis that may be due to an altered energy state.
 ...
PMID:Protein synthesis versus energy state in contracting muscles of perfused rat hindlimb. 672 Aug 85

Escherichia coli 30 S ribosomal subunits undergo a reversible change under low monovalent or divalent cation concentration and become inactive in tRNA binding and 50 S subunit association. In the inactive form, 16 S rRNA base-pairs (921-922).(1395-1396) and (923-925).(1391-1393), which are part of region 28, are unstable and an alternate arrangement, (921-923).(1532-1534), is detected by psoralen photochemical crosslinking. Site-directed mutagenesis has been used to investigate whether changes in base-paired region 28 or the alternate secondary structure is responsible for the inactivity of the subunit. 30 S subunits with the substitution C1533A or with deletion of nucleotides 1534 to 1542 can still be inactivated like the wild-type 30 S subunit. On the other hand, 30 S subunits that contain sequence changes in the 920 to 926 region show moderate to severe decreases in tRNA binding even under activating conditions. When 30 S subunits containing these mutations were subjected to chemical probing, they failed to show the normal hyper-reactivity of nucleotide G926 and, instead, reactivity was shifted to G925 or to G928, and G929. Two mutations in the 920 region result in structures in which A1394 is base-paired rather than being unpaired as normal; deletion but not substitution of A1394 resulted in loss of tRNA binding activity and depression of the reactivity of G926. Mutations were made to insert or delete a nucleotide at position 920. The deletion mutant but not the insertion mutant has decreased tRNA binding activity and also low reactivity of G926. We conclude that structural changes in region 28 account for the active/inactive difference in tRNA binding. Molecular models of region 28 were made using the program MC-SYM. Models that include a hydrogen bond interaction between A1394 and G1392 account for the G926 reactivity in the wild-type sequence and account for the effects of most of the mutations in changing the G926 reactivity.
 ...
PMID:Structural changes in base-paired region 28 in 16 S rRNA close to the decoding region of the 30 S ribosomal subunit are correlated to changes in tRNA binding. 754 48

Neuronal protein synthesis is severely depressed following stress such as heat-shock, hypoxia, and hypoglycemia. Following reversible cerebral ischemia, protein synthesis is transiently inhibited in ischemia-resistant areas, but persistently depressed in vulnerable brain regions. Eukaryotic initiation factor 2 (eIF-2) activity, that is, the formation of the ternary complex eIF-2.GTP.initiator 35S-Met-tRNA, a rate-limiting step in the initiation of cellular protein synthesis, was studied in the rat brain during and following 15 min of transient global cerebral ischemia. At 30 min and 1 hr of reperfusion, a general decrease of eIF-2 activity by approximately 50% was seen in the postmitochondrial supernatant (PMS). In the relatively resistant neocortex and CA3 region of the hippocampus, the eIF-2 activity returns to control levels at 6 hr of reperfusion, but remains depressed in the vulnerable striatum and the CA1 region. Similarly, the activity of the guanine nucleotide exchange factor (GEF), which catalyzes the exchange of GTP for GDP bound to eIF-2, a crucial step for the continued formation of the ternary complex, is transiently reduced in neocortex but persistently depressed in striatum. The postischemic decrease in eIF-2 activity is further attenuated by agarose-bound alkaline phosphatase, and mixing experiments revealed that a vanadate-sensitive phosphatase may be responsible for the depression. Addition of partially purified GEF to PMS from postischemic neocortex restored eIF-2 activity to control levels. We conclude that ischemia alters the balance between phosphorylation and dephosphorylation reactions, leading to an inhibition of GEF and a depression of ternary complex formation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Stress-induced inhibition of protein synthesis initiation: modulation of initiation factor 2 and guanine nucleotide exchange factor activities following transient cerebral ischemia in the rat. 847 77

The complete nucleotide sequence of the mitochondrial genome of the Oriental white stork, Ciconia boyciana, has been determined from captive storks by a novel method incorporating Long PCR and shotgun sequencing. 13 protein-coding genes, two ribosomal RNA genes and 22 transfer RNA genes were identified as in other vertebrate mitochondrial genomes. The position and direction of the NADH6 and tRNA-Glu genes were the same as previously reported for avian mitochondrial genomes. A 71 bp direct repeat and long CAAA repeat sequences were found at the 3' end of the D-loop region, together with SCB-1, SCB-2, SCB-3, and three TAS sequences. Direct sequencing of the PCR fragments in the D-loop region in 26 captive Oriental white storks originating from Japan, China, and Russia revealed nucleotide differences at 18 sites along 1,248 bp, and a total of nine haplotypes have been identified. It was found that one pair of individuals in the Japanese captive breeding program were of the same haplotype, suggesting that they were caught from the same nest. The pair has since been dissolved in consideration of the possibility of inbreeding depression.
 ...
PMID:Determination of the complete nucleotide sequence and haplotypes in the D-loop region of the mitochondrial genome in the oriental white stork, Ciconia boyciana. 1084 18

Novel statistical methods have been developed and used to quantitate and annotate the sequence diversity within combinatorial peptide libraries on the basis of small numbers (1-200) of sequences selected at random from commercially available M13 p3-based phage display libraries. These libraries behave statistically as though they correspond to populations containing roughly 4.0+/-1.6% of the random dodecapeptides and 7.9+/-2.6% of the random constrained heptapeptides that are theoretically possible within the phage populations. Analysis of amino acid residue occurrence patterns shows no demonstrable influence on sequence censorship by Escherichia coli tRNA isoacceptor profiles or either overall codon or Class II codon usage patterns, suggesting no metabolic constraints on recombinant p3 synthesis. There is an overall depression in the occurrence of cysteine, arginine and glycine residues and an overabundance of proline, threonine and histidine residues. The majority of position-dependent amino acid sequence bias is clustered at three positions within the inserted peptides of the dodecapeptide library, +1, +3 and +12 downstream from the signal peptidase cleavage site. Conformational tendency measures of the peptides indicate a significant preference for inserts favoring a beta-turn conformation. The observed protein sequence limitations can primarily be attributed to genetic codon degeneracy and signal peptidase cleavage preferences. These data suggest that for applications in which maximal sequence diversity is essential, such as epitope mapping or novel receptor identification, combinatorial peptide libraries should be constructed using codon-corrected trinucleotide cassettes within vector-host systems designed to minimize morphogenesis-related censorship.
 ...
PMID:Quantitative assessment of peptide sequence diversity in M13 combinatorial peptide phage display libraries. 1236 27

D-Tyr-tRNA(Tyr) deacylase is an editing enzyme that removes d-tyrosine and other d-amino acids from charged tRNAs, thereby preventing incorrect incorporation of d-amino acids into proteins. A model for the catalytic mechanism of this enzyme is proposed based on the crystal structure of the enzyme from Haemophilus influenzae determined at a 1.64-A resolution. Structural comparison of this dimeric enzyme with the very similar structure of the enzyme from Escherichia coli together with sequence analyses indicate that the active site is located in the dimer interface within a depression that includes an invariant threonine residue, Thr-80. The active site contains an oxyanion hole formed by the main chain nitrogen atoms of Thr-80 and Phe-79 and the side chain amide group of the invariant Gln-78. The Michaelis complex between the enzyme and D-Tyr-tRNA was modeled assuming a nucleophilic attack on the carbonyl carbon of D-Tyr by the Thr-80 O(gamma) atom and a role for the oxyanion hole in stabilizing the negatively charged tetrahedral transition states. The model is consistent with all of the available data on substrate specificity. Based on this model, we propose a substrate-assisted acylation/deacylation-catalytic mechanism in which the amino group of the D-Tyr is deprotonated and serves as the general base.
 ...
PMID:A catalytic mechanism for D-Tyr-tRNATyr deacylase based on the crystal structure of Hemophilus influenzae HI0670. 1257 Dec 43


1 2 Next >>